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Related Collections Immunobiology Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 April 2001, Vol. 97, No. 7, pp. 2067-2074 IMMUNOBIOLOGY TRAIL expression by activated human CD4+V24NKT cells induces in vitro and in vivo apoptosis of human acute myeloid leukemia cells Mie Nieda, Andrew Nicol, Yashuhiko Koezuka, Akiko Kikuchi, Natalia Lapteva, Yuji Tanaka, Katsushi Tokunaga, Kenji Suzuki, Nobuhiko Kayagaki, Hideo Yagita, Hisamaru Hirai, and Takeo Juji From the Department of Research of the Japanese Red Cross Central Blood Center; Japanase Red Cross Hospital; Department of Human Genetics and Department of Hematology and Oncology, Graduate School of Medicine; Department of Immunology, Juntendo University School of Medicine; Tokyo, Japan; Queensland Institute of Medical Research and Department of Medicine, University of Queensland, Australia; Royal Brisbane Hospital, Brisbane, Australia; and Pharmaceutical Research Laboratory, Kirin Brewery, Gunma, Japan. Human V24NKT cells are activated by -galactosylceramide (-GalCer)-pulsed dendritic cells in a CD1d-dependent and a T-cell receptor-mediated manner. Here, we demonstrate that CD4+V24NKT cells derived from a patient with acute myeloid leukemia (AML) M4 are phenotypically similar to those of healthy donors and, in common with those derived from healthy donors, express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) when the cells are activated by -GalCer-pulsed dendritic cells but not prior to activation. We also show that myeloid leukemia cells from patients with AML M4, but not from patients with AML M0 or M1, undergo apoptosis following culture with TRAIL-expressing autologous or allogeneic healthy donor V24NKT cells. Apoptosis of AML M4 leukemia cells from patient peripheral blood was almost completely blocked by a neutralizing monoclonal antibody against TRAIL, indicating that TRAIL on V24NKT cells is essential for the induction of apoptosis in AML M4 leukemia cells. A nonobese diabetic-severe combined immunodeficient human leukemia (AML M4) model showed that human activated CD4+V24NKT cells induced apoptosis of human leukemia cells in vivo. This is the first evidence that activated V24NKT cells express TRAIL and that TRAIL causes apoptosis of monocytic leukemia cells from patients with AML M4 in vitro and in vivo. Adoptive immune therapy with activated V24NKT cells, or other strategies to increase activated V24NKT cells in vivo, may be of benefit to patients with AML M4. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Azakami, T. Sato, N. Araya, A. Utsunomiya, R. Kubota, K. Suzuki, D. Hasegawa, T. Izumi, H. Fujita, S. Aratani, et al. Severe loss of invariant NKT cells exhibiting anti-HTLV-1 activity in patients with HTLV-1-associated disorders Blood, October 8, 2009; 114(15): 3208 - 3215. 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